High-fat Diet-induced Obese Mice Research Articles

Mechanism of Xianglian Pills in improving dyslipidemia in obese mice induced by high-fat diet based on network pharmacology and intestinal flora

The present study aimed to investigate the effect of Xianglian Pills(XLP) on lipid metabolism in obese mice and explore the underlying mechanism based on network pharmacology and intestinal flora. Firstly, network pharmacology was used to predict the possible effect of XLP on obesity. Secondly, an obese mouse model induced by a high-fat diet was established to observe changes in mouse body weight, adiposity index, liver and adipose tissue pathology. Lipid profiles, liver and kidney function markers, insulin content, and the expression of recombinant uncoupling protein 1(UCP-1) and PR structural domain protein 16(PRDM16) were measured. The 16S rRNA gene sequencing technology was used to analyze the changes in the intestinal flora. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that XLP mainly played a role in improving obesity by regulating lipolysis, type 2 diabetes mellitus, and insulin resistance. The results of animal experiments showed that XLP significantly reduced body weight, adiposity, blood lipid levels, and serum insulin levels in obese mice, while enhancing the expression of UCP-1 and PRDM16 in adipose tissue without causing damage to the liver or kidneys. The 16S rRNA gene sequencing results showed that XLP decreased the Firmicutes/Bacteroidetes(F/B) ratio at the phylum level, increased the relative abundance of Akkermansia and Bacteroides at the family and genus levels, and reduced the abundance of Allobaculum. Therefore, XLP can effectively improve lipid metabolism disorders in high-fat diet-induced obese mice, and the mechanism is related to the improvement of brown adipose function, the browning of white fat, the accelerated lipid metabolism, and the improvement of intestinal flora. However, its effect on promoting the conversion of white adipose to brown adipose still needs to be further studied.

Novel Lauric Acid-Butyric Structural Lipid Inhibits Inflammation: Small Intestinal Microbes May Be Important Mediators.

Butyric acid (C4) and lauric acid (C12) are recognized as functional fatty acids, while the health benefits of the structural lipids they constitute remain unclear. In this study, lauric acid-butyric structural lipid (SLBL ) is synthesized through ultrasound-assisted enzyme-catalyzed acidolysis and its health benefits are evaluated in a high-fat diet-induced obesity mouse model. SLBL and its physical mixture (MLBL ) do not significantly inhibit obesity in mice. However, SLBL treatment increases the ratio of n3/n6 fatty acids in the liver and improves obesity-induced hepatic lipid metabolism disorders. Furthermore, the expression of liver pro-inflammatory cytokines (interleukin [IL]-6, IL-1β, TNF-α) are significantly suppressed by SLBL , while the expression of anti-inflammatory cytokine (IL-10) is increased. Moreover, SLBL ameliorates the dysbiosis of small intestinal microbes induced by high-fat diet and regulates microbial community structure to be close to the control group. Especially, SLBL significantly alleviates the high-fat diet-induced decrease in Dubosiella and Bifidobacterium abundance. Correlation analysis reveals that SLBL treatment increases the abundance of microorganisms with potential anti-inflammatory function and decreases the abundance of potentially pathogenic bacteria. In all, small intestinal microbes may be a significant bridge for the positive anti-inflammatory effects of SLBL , while the exact mechanism remains to be clarified.

Diet Change Improves Obesity and Lipid Deposition in High-Fat Diet-Induced Mice

The number of obese people is increasing dramatically worldwide, and one of the major causes of obesity is excess energy due to high-fat diets. Several studies have shown that reducing food and energy intake represents a key intervention or treatment to combat overweight/obesity. Here, we conducted a 12-week energy-restricted dietary intervention for high-fat diet-induced obese mice (C57BL/6J) to investigate the effectiveness of diet change in improving obesity. The results revealed that the diet change from HFD to NFD significantly reduced weight gain and subcutaneous adipose tissue weight in high-fat diet-induced obese mice, providing scientific evidence for the effectiveness of diet change in improving body weight and fat deposition in obese individuals. Regarding the potential explanations for these observations, weight reduction may be attributed to the excessive enlargement of adipocytes in the white adipose tissue of obese mice that were inhibited. Diet change significantly promoted lipolysis in the adipose tissue (eWAT: Adrb3, Plin1, HSL, and CPTA1a; ingWAT: CPT1a) and liver (reduced content of nonesterified fatty acids), and reduced lipogenesis in ingWAT (Dgat2). Moreover, the proportion of proliferative stem cells in vWAT and sWAT changed dramatically with diet change. Overall, our study reveals the phenotypic, structural, and metabolic diversity of multiple tissues (vWAT and sWAT) in response to diet change and identifies a role for adipocyte stem cells in the tissue specificity of diet change.

The effects of Glycyrrhiza Glabra extract in high-fat diet-induced obese male mice: A controlled experimental study

AimsThis study sought to evaluate anti-obesity effects, improved metabolic function, and spermatogenesis of Licorice root extract at doses of 343 mg/kg and 686 mg/kg. MethodsThis was a controlled experimental, descriptive cross-sectional, longitudinal study follow-up over 10 weeks of nourishment. We generated an obesity model in white mice (Swiss albino) in 6 weeks with a high-fat diet (52–53% lipid, 610 Kcal/100g). Besides, the hydroethanolic extract of Radix Glycyrrhizae (RG) was prepared. Then, we divided mice into 4 groups (NFD, HFD, RG343, RG686) with 12 mice/group. We followed morphological indices, metabolic function, and spermatogenesis after 4 weeks of taking this extract. ResultsFollowing the intervention, mice exhibited reduced weight, weight gain, BMI, and waist circumference. However, there was no difference between the 2 doses. Moreover, blood glucose, visceral fat mass, total cholesterol, and LDL-c levels of mice after the intervention were lower. Furthermore, there was a clear difference between the two doses. After the intervention, mice had larger penis, testes, epididymis, and seminal vesicle diameters and improved semen parameters, noting the difference between the two doses. ConclusionLicorice root extract helps to reduce weight, BMI, and visceral fat and improve metabolic function and spermatogenesis of obese mice. Significantly, the dose of 686 mg/kg was more effective than the dose of 343 mg/kg.

Thrombospondin1 antagonist peptide treatment attenuates obesity-associated chronic inflammation and metabolic disorders in a diet-induced obese mouse model

Thrombospondin1 (TSP1) is a multifunctional matricellular protein. Previously, we demonstrated that TSP1 plays a pivotal role in obesity-related inflammation and insulin resistance (IR) by modulating macrophage accumulation and activation in adipose tissue. Moreover, in our in vitro studies, a CD36-derived peptide, functioning as a TSP1 antagonist, effectively inhibited TSP1-induced proinflammatory macrophage activation. However, whether this CD36 peptide can inhibit obesity-induced inflammation and IR in vivo is unknown and determined in this study in a high fat diet-induced obese mouse model (DIO). CD36 peptide or control peptide was intraperitoneally administered into the established obese mice triweekly for 6 weeks. We found that CD36 peptide treatment didn’t affect obesity or weight gain but significantly reduced proinflammatory cytokine production systemically and in visceral fat tissue. Adipose tissue exhibited fewer crown-like structures and reduced macrophage infiltration. CD36 peptide treatment also attenuated the proinflammatory phenotype of bone marrow derived macrophages from obese mice. Furthermore, CD36 peptide treatment improved glucose tolerance and insulin sensitivity, and mitigated obesity-related fatty liver disease and kidney damage. Collectively, this study suggests that the CD36 peptide, as a TSP1 antagonist, shows promise as a novel therapeutic approach for managing obesity-related metabolic disorders.

Fuzhuan brick tea extract ameliorates obesity-induced skeletal muscle atrophy by alleviating mitochondrial dysfunction in mice

Fuzhuan brick tea (FBT) is a post-fermented tea fermented by the fungus Eurotium cristatum and is mainly produced in Hunan Province, China. Our previous study revealed that FBT extract prevents obesity by increasing energy expenditure and mitochondrial content in mice. Therefore, in this study, we hypothesized that FBT extract could be effective in alleviating obesity-induced muscle atrophy by addressing mitochondrial dysfunction, and aimed to explore the underlying molecular mechanism of FBT extract in high-fat diet-induced obese mice. FBT extract increased skeletal muscle weight and size, myosin heavy chain isoforms, and muscle performance in obese mice. Additionally, FBT extract reduced obesity-induced intramuscular lipids, skeletal muscle inflammation, and the expression of skeletal muscle atrophy markers, and increased the expression of fibronectin type III domain-containing protein 5 in skeletal muscles. Obesity-induced skeletal muscle mitochondrial dysfunction was improved by FBT extract as analyzed through mitochondrial morphology, fatty acid oxidation, respiratory chain complexes, and mitochondrial dynamics and biogenesis. Epigallocatechin, a major bioactive compound in FBT extract, attenuated palmitic acid-induced muscle atrophy by regulating mitochondrial functions in C2C12 cells. In conclusion, FBT extract may prevent obesity-induced muscle atrophy by alleviating mitochondrial dysfunction in mice.

Surface-exposed chaperonin 60 derived from Propionibacterium freudenreichii MJ2 inhibits adipogenesis by decreasing the expression of C/EBPα/PPARγ

Recent studies have shown that the health benefits of probiotics are not limited to those offered by living bacteria. It was reported that both live and killed cells of Propionibacterium freudenreichii MJ2 (MJ2) isolated from raw milk showed antiobesity activity in 3T3-L1 cells and high-fat diet-induced obese mice. This study was aimed at identifying the active component(s) responsible for the antiadipogenic activity of MJ2. Cell wall, surface protein, and cytoplasmic fractions of MJ2 were investigated for their inhibitory effects on adipogenesis in 3T3-L1 cells. Adipocytes treated with the surface protein fraction showed significantly lower lipid accumulation. Using the MASCOT algorithm following LC-MS/MS analysis, 131 surface proteins were identified and they were principally classified into three categories (network clusters related to ribosomes, carbon metabolism, and chaperones). Among them, chaperonin 60 (Cpn60) was selected as a potential candidate protein. Cpn60 inhibited lipid accumulation and adipogenesis during the early period of differentiation (days 0–2) and decreased expression of genes related to adipogenesis (Pparg and Cebpa) and lipogenesis (Fas and Scd1). The expression of Gata2/3, which suppresses adipogenesis, significantly increased in Cpn60-treated cells. Moreover, the nuclear translocation of C/EBPβ was inhibited by Cpn60 treatment. In conclusion, Cpn60, a surface protein in MJ2, shows antiadipogenic activity by reducing the expression of C/EBPβ through the upregulation of Gata2/3 expression followed by downregulation of Pparg and Cebpa expression.

Alternate-day fasting ameliorated anxiety-like behavior in high-fat diet-induced obese mice

Alternate-day fasting (ADF) has been reported to reduce body weight, neuroinflammation, and oxidative stress damage. However, it is not known whether ADF affects obesity-induced anxiety-like behavior. Here, male C57BL/6 mice were given an alternate fasting and high-fat diet (HFD) or standard chow diet (SD) every other day for 16 or 5 weeks. After the intervention, the degree of anxiety of the mice was evaluated by the open field test (OFT) and the elevated plus maze (EPM) test. Pathological changes in the hippocampus, the expression of Sirt1 and its downstream protein monoamine oxidase A (MAO-A) in the hippocampus, and the expression of 5-hydroxytryptamine (5-HT) were detected. Compared with HFD-fed mice, HFD-fed mice subjected to ADF for 16 weeks had a lower body weight but more brown adipose tissue (BAT), less anxiety behavior, and less pathological damage in the hippocampus, and lower expression of Sirt1 and MAO-A protein and higher 5-HT levels in the hippocampus could be observed. In addition, we noted that long-term ADF intervention could cause anxiety-like behavior in SD mice. Next, we changed the intervention time to 5 weeks. The results showed that short-term ADF intervention could reduce the body weight and increase the BAT mass of SD mice, but it did not affect anxiety. These results indicated that long-term ADF ameliorated obesity-induced anxiety-like behavior and hippocampal damage, but caused anxiety in normal-weight mice. Short-term ADF did not produce adverse emotional reactions in normal-weight mice. Here, we might provide new ideas for the treatment of obesity-induced anxiety.

Effects of diallyl disulfide administration on insulin resistance in high-fat diet-fed mice

ObjectivesDiallyl disulfide (DADS) is a natural organosulfur compound found in garlic and related plants with various pharmacologic effects. However, whether DADS improves obesity-induced insulin resistance (IR) and its underlying mechanisms remain unclear. The aim of this study was to investigate the effects of DADS on systemic IR in high-fat diet-induced obese mice. MethodsTo induce obesity, 8-wk-old male C57BL/6J mice were fed a high-fat diet (60% fat/kcal). The mice were assigned to three weight-matched groups: control (CON, n = 8), low-dose DADS (DADS-L, n = 8), and high-dose DADS (DADS-H, n = 9). The treated mice were orally administered DADS (25 or 100 mg/kg) 5 d/wk for 8 wk. At 15 wk of age, an intraperitoneal glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed. Twenty-four hours after the final administration of DADS, epididymal fat and the liver were sampled after a 5-h fast. ResultsDADS administration significantly attenuated body and fat weight gains during the experimental period. Additionally, systemic IR, as evaluated by ITT, was significantly improved by DADS administration in a dose-dependent manner. High-dose DADS administration significantly decreased liver triacylglycerol levels. Moreover, high-dose DADS administration decreased the c-Jun N-terminal kinase (JNK) phosphorylation and significantly increased heat shock protein 72 expression in the liver. ConclusionsThe results of this study suggested that DADS administration alleviated systemic IR in obese mice. This may be associated with decreased hepatic fat accumulation and a heat shock protein 72-mediated decrease in JNK activity in the liver.

The ethanolic extract of Korean Curcuma longa rhizome inhibits adipogenesis in 3T3-L1 adipocytes and high-fat diet-induced obese mice via activating AMPK signaling pathway

The present study aimed to evaluate the anti-obesity effect of the ethanolic extract of Korean Curcuma longa (CLE) on 3T3-L1 adipocytes and high-fat diet (HFD)-induced obesity in mouse. CLE treatment suppressed lipid accumulation and restored the differentiation-induced changes in adipogenesis- and lipolysis-related proteins by recovering phosphorylation of AMP-activated protein kinase (AMPK). Moreover, in CLE-administered HFD-induced mouse model, body weight and lipid accumulation were reduced, and the changes in factors related to adipogenesis and lipolysis were regulated in the adipose and liver tissues, confirming that these effects were due to a restoration in the phosphorylation of AMPK. In summary, these results provide important insights into the anti-obesity role of CLE by demonstrating its anti-obesity effects on adipocytes and obese mouse models, thereby suggesting the potential application of CLE as a preventive agent for obesity.

Glutamine Ameliorates Liver Steatosis via Regulation of Glycolipid Metabolism and Gut Microbiota in High-Fat Diet-Induced Obese Mice.

Obesity and its associated conditions, such as nonalcoholic fatty liver disease (NAFLD), are risk factors for health. The aim of this study was to explore the effects of glutamine (Gln) on liver steatosis induced by a high-fat diet (HFD) and HEPG2 cells induced by oleic acid. Gln demonstrated a positive influence on hepatic homeostasis by suppressing acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) and promoting sirtuin 1 (SIRT1) expression while improving glucose metabolism by regulating serine/threonine protein kinase (AKT)/factor forkhead box O1 (FOXO1) signals in vivo and in vitro. Obese Gln-fed mice had higher colonic short-chain fatty acid (SCFA) contents and lower inflammation factor protein levels in the liver, HEPG2 cells, and jejunum. Gln-treated obese mice had an effective decrease in Firmicutes abundance. These findings indicate that Gln serves as a nutritional tool in managing obesity and related disorders.

Fucoxanthin extract ameliorates obesity associated with modulation of bile acid metabolism and gut microbiota in high-fat-diet fed mice.

Fucoxanthin extract (FX) is a type of carotenoid with a beneficial effect against obesity. The purpose of this study was to explore its precise action mechanism of losing weight. A high-fat diet induced obesity mouse model was established to study the effects of different doses of FX on C57BL/6J male mice for 12weeks. Following intervention, serum indices, tissue sections, liver gene expression, and intestinal microorganisms were analyzed. FX at low, medium, and high dosages (80, 160, and 320mg/kg/day, respectively) for 12weeks was associated with the lower body weight of mice when compared to that of high-fat-diet fed mice. It also improved glucose tolerance as well as serum lipid levels, and reduced fat accumulation. Significant regulation of bile acid metabolism and intestinal microbiota may contribute to the above effects. The bile acids in the FXH group were significantly increased. A low-dose and a medium-dose FX increased the level of transmembrane G protein-coupled receptor 5 (TGR5); a low-dose and high-dose FX increased the farnesoid X receptor (FXR) expression, and a medium-dose had no effect. 16S rRNA sequencing indicated that the Lachnospiraceae and Oscillospiraceae contributed to the beneficial effects of FX. Our study sheds light on mechanisms behind the weight-lowering of FX, and manifested that bile acid metabolism and gut microbiota may be potential therapies. These results support that FX is a valuable candidate for promoting health and alleviating obesity.

Effect of (poly)phenol-rich ‘Daux Belan’ apple supplementation on diet-induced obesity and glucose intolerance in C57BL/6NCrl mice

Obesity is a state of metabolic dysfunction that can lead to dyslipidemia and impaired glucose homeostasis. Apple polyphenols have been shown to ameliorate dyslipidemia/metabolic dysfunction in humans. The influence of apple (poly)phenols on energy metabolism in high-fat (HF) diet-induced obese mice remains controversial. This study examined the effect of dietary supplementation of (poly)phenol-rich ‘Daux Belan’ apple (DB; 6.2 mg gallic acid equivalence (GAE)/mouse/day; 0.15% (poly)phenol) in the form of freeze-dried powder on glucose and lipid metabolism in male HF-fed C57BL/6NCrl mice, in comparison to low-(poly)phenol-containing ‘Zestar’ apple (Z; 0.4 mg GAE/mouse/day). Obesity, glucose intolerance, hypertriglyceridemia, and hepatic lipid vacuolation were induced by HF feeding while circulating cholesterol levels remained unchanged. DB apple supplementation did not protect against HF-induced body weight gain, hyperglycemia, hepatic triglyceride level elevation, and hepatic lipid vacuolation at the tested dosage. Future studies should be conducted with increased DB dosage and employ apple (poly)phenols supplemented in the form of extracts or sugar-free powder.

Probiotic-fermented tomato alleviates high-fat diet-induced obesity in mice: Insights from microbiome and metabolomics

Probiotic-fermented plant-based foods are associated with weight loss. Here, we hypothesized probiotic-fermented tomato (FT) as a functional food with potential to alleviate obesity, thus the obesity-alleviating effects and mechanisms of FT on high-fat diet-induced obese mice were explored via biochemical, gut microbiome, and serum metabolomics analysis. The results showed that FT performed better than unfermented tomato in reducing body weight gain and fat accumulation, improving dyslipidemia and glucose homeostasis, and relieving inflammation and adipocytokine dysregulation. Particularly, live probiotic-fermented tomato (LFT) was associated with improved diversity, composition, and structure of gut microbiota, suppressed obesity-related genera growth (e.g., Clostridium, Olsenella, and Mucispirillum), and promoted beneficial genera growth (e.g., Roseburia, Coprococcus, and Oscillospira), which were associated negatively with body weight, TC, TG, and TNF-α levels. Additionally, LFT was associated with positive changes in glycerophospholipids, sphingolipids, unsaturated fatty acids, and amino acids levels. Collectively, as a functional food, LFT possessed potential for obesity alleviation.

Short term effect of tetrahydrocurcumin on adipose angiogenesis in very high-fat diet-induced obesity mouse model.

Tetrahydrocurcumin (THC) has been shown to possess anti-angiogenic activities. This study aims to investigate the effects of THC on adipose angiogenesis and expression of angiogenic factors that occurs in 60% high-fat diet-induced obese mice. Male ICR mice were randomly divided into 3 groups: mice fed with a low-fat diet (LFD group); mice fed with very high fat diet (VHFD group), and mice fed with VHFD supplemented with THC (300 mg/kg/day orally) (VHFD+THC treated group) for 6 weeks. Body weight (BW), food intake, fasting blood sugar (FBS), lipid profiles and visceral fats weight (VF) were measured. The microvascular density (MVD), TNF-α, VEGF, MMP-2, and MMP-9 expressions were evaluated. The VHFD group had significantly increased total cholesterol, triglyceride, food intake, BW, VF, VF/BW ratio, adipocyte size and the number of crown-liked structures as compared to LFD group. THC supplementation markedly reduced these parameters and adipocyte hypertrophy and inflammation in white adipose tissues. MVD, TNF-α, VEGF, MMP-2, and MMP-9 were over-expressed in the VHFD group. However, THC supplementation decreased MVD and reduced expression of TNF-α, VEGF, MMP-2, and MMP-9. In conclusion, THC suppressed angiogenesis in adipose tissue by the downregulation of TNF-α, VEGF, MMP-2, and MMP-9. With its effects on lipid metabolism as well as on food consumption, THC could contribute to lower visceral fat and body weight. Overall, our study demonstrated the potential benefit of THC in mitigating obesity and associated metabolic disorders along with elucidated the suppression of adipose angiogenesis as one of its underlying mechanisms.

DHA alleviated hepatic and adipose inflammation with increased adipocyte browning in high-fat diet-induced obese mice

Obesity is associated with accumulation of inflammatory immune cells in white adipose tissue, whereas thermogenic browning adipose tissue is inhibited. Dietary fatty acids are important nutritional components and several clinical and experimental studies have reported beneficial effects of docosahexaenoic acid (DHA) on obesity-related metabolic changes. In this study, we investigated effects of DHA on hepatic and adipose inflammation and adipocyte browning in high-fat diet-induced obese C57BL/6J mice, and in vitro 3T3-L1 preadipocyte differentiation. Since visceral white adipose tissue has a close link with metabolic abnormality, epididymal adipose tissue represents current target for evaluation. A course of 8-week DHA supplementation improved common phenotypes of obesity, including improvement of insulin resistance, inhibition of macrophage M1 polarization, and preservation of macrophage M2 polarization in hepatic and adipose tissues. Moreover, dysregulated adipokines and impaired thermogenic and browning molecules, considered obesogenic mechanisms, were improved by DHA, along with parallel alleviation of endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and mitochondrial DNA stress-directed innate immunity. During 3T3-L1 preadipocytes differentiation, DHA treatment decreased lipid droplet accumulation and increased the levels of thermogenic, browning, and mitochondrial biogenesis molecules. Our study provides experimental evidence that DHA mitigates obesity-associated inflammation and induces browning of adipose tissue in visceral epididymal adipose tissue. Since obesity is associated with metabolic abnormalities across tissues, our findings indicate that DHA may have potential as part of a dietary intervention to combat obesity.

How hypoxia affects microbiota metabolism in mice.

To investigate the relationship between gut microbiota and the fecal metabolites of hypoxic environments in mice. High-fat diet-induced obese mice (n = 20) and normal diet-fed mice (n = 20) were randomly divided into four groups: high altitude obese group (HOB), high altitude normal weight group (HN), low altitude obese group LOB (LOB), and low altitude normal weight group (LN). Fecal samples from each group were 16S rRNA gene sequenced, and five samples from each of the four groups above were selected for non-targeted fecal metabolomics analysis using liquid chromatography-mass spectrometry. The relationship between gut microbiota and fecal metabolites was analyzed using SIMCA 14.1, MetaboAnalyst 5.0 and R 4.1.11. (A) Body weight was significantly lower in the hypoxic obesity group than in the normoxic obesity group. (B) Differences in α-diversity and β-diversity were found in the fecal gut microbiota of mice of different body weights and altitude, and the diversity of gut microbiota was higher in the normal group than in the obese group; the results of the comparison between the two groups showed that Faecalibaculum, Romboutsia, Lactobacillus, and A2 were associated with obesity; Romboutsia was associated with hypoxia. (C) The metabolic profiles of fecal metabolites differed between groups: gut microbiota were associated with nucleotide and amino acid metabolism in the same body groups, while gut microbiota were associated with lipid and amino acid metabolism in the same oxygen concentration groups. (a) Gut microbiota diversity was reduced in obese groups. Romboutsia was the dominant microbiota in the hypoxia group. (b) Gut microbiota were associated with nucleotide and amino acid metabolism in the same body weight groups, while they were associated with lipid and amino acid metabolism in the same altitude groups.

Single-Cell Hemoprotein Diet Changes Adipose Tissue Distributions and Re-Shapes Gut Microbiota in High-Fat Diet-Induced Obese Mice.

We have previously observed that feeding with single-cell hemoprotein (heme-SCP) in dogs (1 g/day for 6 days) and broiler chickens (1 ppm for 32 days) increased the proportion of lactic acid bacteria in the gut while reducing their body weights by approximately 1~2%. To define the roles of heme-SCP in modulating body weight and gut microbiota, obese C57BL/6N mice were administered varied heme-SCP concentrations (0, 0.05, and 0.5% heme-SCP in high fat diet) for 28 days. The heme-SCP diet seemed to restrain weight gain till day 14, but the mice gained weight again later, showing no significant differences in weight. However, the heme-SCP-fed mice had stiffer and oilier bodies compared with those of the control mice, which had flabby bodies and dull coats. When mice were dissected at day 10, the obese mice fed with heme-SCP exhibited a reduction in subcutaneous fat with an increase in muscle mass. The effect of heme-SCP on the obesity-associated dyslipidemia tended to be corroborated by the blood parameters (triglyceride, total cholesterol, and C-reactive protein) at day 10, though the correlation was not clear at day 28. Notably, the heme-SCP diet altered gut microbiota, leading to the proliferation of known anti-obesity biomarkers such as Akkermansia, Alistipes, Oscillibacter, Ruminococcus, Roseburia, and Faecalibacterium. This study suggests the potential of heme-SCP as an anti-obesity supplement, which modulates serum biochemistry and gut microbiota in high-fat diet-induced obese mice.

A natural Nrf2 activator glucoraphanin improves hepatic steatosis in high-fat diet-induced obese male mice associated with AMPK activation.

The online version contains supplementary material available at 10.1007/s13340-023-00658-6.

Oral Semaglutide under Human Protocols and Doses Regulates Food Intake, Body Weight, and Glycemia in Diet-Induced Obese Mice.

The first oral form of the glucagon-like peptide-1 receptor agonist, oral semaglutide, has recently been launched and potently controls glycemia and body weight in subjects with type 2 diabetes. This drug carries the absorption enhancer and requires specific protocols of administration. The mechanism of action of oral semaglutide is not fully understood, for which an appropriate experimental model is required. This study explores the metabolic effects of oral semaglutide in mice under human protocols and doses. Oral semaglutide was bolus and once daily injected into high-fat diet-induced obese (DIO) mice under human protocols, followed by monitoring blood glucose, food intake, and body weight. Oral semaglutide 0.23 mg/kg, a comparable human dose (14 mg) in a small volume of water under human protocols rapidly decreased blood glucose and food intake and continuously reduced food intake and weight gain for 3 days in DIO mice. At 0.7 mg/kg (42 mg), this drug was somewhat more potent. Oral semaglutide with human protocols and doses rapidly reduces blood glucose and food intake and continuously suppresses feeding and weight in DIO mice. This study establishes mice as a model suitable for analyzing the mechanism of anti-obesity/diabetes actions of oral semaglutide.